EXTENDED ABSORPTION OF LIOTHYRONINE FROM POLY-ZINC-LIOTHYRONINE (PZL): RESULTS FROM A PHASE 1, STUDY IN HUMANS

[helvella]

Very small, very early trial. At least none of the 12 healthy volunteers seemed have an awful time.

Thyroid. 2021 Oct 12.

doi: 10.1089/thy.2021.0304. Online ahead of print.

EXTENDED ABSORPTION OF LIOTHYRONINE FROM POLY-ZINC-LIOTHYRONINE (PZL): RESULTS FROM A PHASE 1, DOUBLE-BLIND, RANDOMIZED, AND CONTROLLED STUDY IN HUMANS

Alexandra M Dumitrescu 1 , Erin C Hanlon 2 , Marilyn Arosemena 3 , Olga Duchon 4 , Matthew D Ettleson 5 , Mihai Giurcanu 6 , Antonio Carlos Bianco 7

Affiliations

PMID: 34641706 DOI: 10.1089/thy.2021.0304

Abstract

Background: Liothyronine (LT3) has been increasingly used in combination with levothyroxine (LT4) in the treatment of hypothyroidism. A metal coordinated form of LT3, known as poly-zinc-liothyronine (PZL), avoided in rats the typical T3 peak seen after oral administration of LT3.

Objectives: To evaluate in healthy volunteers (i) the pharmacokinetics of PZL-derived T3 after a single dose, (ii) the pharmacodynamics of PZL-derived T3, (iii) incidence of adverse events; (iv) exploratory analysis of the sleep patterns after LT3, PZL or placebo administration.

Methods: 12 healthy volunteers 18 to 50 years of age were recruited for a Phase 1, double-blind, randomized, single-dose placebo-controlled, cross-over study to compare PZL against LT3 or placebo. Subjects were admitted three separate times to receive a randomly assigned capsule containing placebo, 50-mcg LT3, or 50-mcg-PZL, and were observed for 48h. A 2-week washout period separated each admission.

Results: LT3-derived serum T3 levels exhibited the expected profile, with a Tmax at 2h and return to basal levels by 24-36h. PZL-derived serum T3 levels exhibited a ~30% lower Cmax that was 1 h delayed and extended into a plateau that lasted up to 6h. This was followed by a lower but much longer plateau; by 24h serum, T3 levels still exceeded ½ of Cmax. TSH levels were similarly reduced in both groups.

Conclusion: PZL possesses the necessary properties to achieve a much improved T3 pharmacokinetic. Drug product development of PZL should improve the delivery of T3 even further. PZL is on track to provide hypothyroid patients with stable levels of serum T3.

As almost always, the full paper is behind a paywall.

pubmed.ncbi.nlm.nih.gov/346...

diogenes

[TSH110]

Thanks for posting.Let’s hope hypothyroid patients can get their mitts on it, if it’s approved.

[helvella Administrator in reply to TSH110]

I just hope it isn't being hyped up too much and it ends up with lots of us being very disappointed.

[TSH110 in reply to helvella]

Quite - but its good to know that they are working on it

[helvella Administrator in reply to TSH110]

Even if this attempt ends in failure, I do think there is every possibility of something else coming along. Just might take quite a number of years.

[JGBH]

Thanks for this information. Keeping fingers crossed!

[Zephyrbear]

Why do they use “healthy” subjects who, presumably have equally healthy thyroids that will adjust their output accordingly? Why not use subjects in their studies, especially on such a small scale, who would need such medication and whose compromised thyroids would not make up that difference?

Surely that would give a more realistic answer…

[helvella Administrator in reply to Zephyrbear]

Because at this stage they need to both see whether anyone has side effects and what happens!

Phase: 1

Number and type of subject : 50−200

healthy subjects (usually) or patients

who are not expected to benefit from

the IMP

Questions:

• Is the IMP safe in humans?

• What does the body do to the IMP?

(pharmacokinetics)

• What does the IMP do to the body?

(pharmacodynamics)

• Might the IMP work in patients?

abpi.org.uk/media/1627/guid...

What we do not know, from what I can access, is whether they were all male - as so often has been the case.

[diogenes Remembering]

Have requested full paper for access here

[helvella Administrator in reply to diogenes]

Thank you.

[diogenes Remembering in reply to helvella]

Full paper sent on to Lyn Mynott.

[Radio2]

Thank you for posting this Helvella, this looks likely to be more stable than current medications. Fingers crossed for years to come - very promising.